What is jaundice?

Jaundice is not a disease but rather a sign that can occur in many different diseases. Jaundice is the
yellowish staining of the skin and sclerae (the whites of the eyes) that is caused by high levels in blood of
the chemical bilirubin. The color of the skin and sclerae vary depending on the level of bilirubin. When
the bilirubin level is mildly elevated, they are yellowish. When the bilirubin level is high, they tend to be
brown.
What causes jaundice?
Bilirubin comes from red blood cells. When red blood cells get old, they are destroyed. Hemoglobin, the
iron-containing chemical in red blood cells that carries oxygen, is released from the destroyed red blood
cells after the iron it contains is removed. The chemical that remains in the blood after the iron is removed
becomes bilirubin.
The liver has many functions. One of the liver's functions is to produce and secrete bile into the intestines
to help digest dietary fat. Another is to remove toxic chemicals or waste products from the blood, and
bilirubin is a waste product. The liver removes bilirubin from the blood. After the bilirubin has entered the
liver cells, the cells conjugate (attaching other chemicals, primarily glucuronic acid) to the bilirubin, and
then secrete the bilirubin/glucuronic acid complex into bile. The complex that is secreted in bile is called
conjugated bilirubin. The conjugated bilirubin is eliminated in the feces. (Bilirubin is what gives feces its
brown color.) Conjugated bilirubin is distinguished from the bilirubin that is released from the red blood
cells and not yet removed from the blood which is termed unconjugated bilirubin.
Jaundice occurs when there is 1) too much bilirubin being produced for the liver to remove from the
blood. (For example, patients with hemolytic anemia have an abnormally rapid rate of destruction of their
red blood cells that releases large amounts of bilirubin into the blood), 2) a defect in the liver that prevents
bilirubin from being removed from the blood, converted to bilirubin/glucuronic acid (conjugated) or
secreted in bile, or 3) blockage of the bile ducts that decreases the flow of bile and bilirubin from the liver
into the intestines. (For example, the bile ducts can be blocked by cancers, gallstones, or inflammation of
the bile ducts). The decreased conjugation, secretion, or flow of bile that can result in jaundice is referred
to as cholestasis: however, cholestasis does not always result in jaundice.
What problems does jaundice cause?
Jaundice or cholestasis, by themselves, causes few problems (except in the newborn, and jaundice in the
newborn is different than most other types of jaundice, as discussed later.) Jaundice can turn the skin and
sclerae yellow. In addition, stool can become light in color, even clay-colored because of the absence of
bilirubin that normally gives stool its brown color. The urine may turn dark or brownish in color. This
occurs when the bilirubin that is building up in the blood begins to be excreted from the body in the urine.
Just as in feces, the bilirubin turns the urine brown.
Besides the cosmetic issues of looking yellow and having dark urine and light stools, the symptom that is
associated most frequently associated with jaundice or cholestasis is itching, medically known as pruritus.
The itching associated with jaundice and cholestasis can sometimes be so severe that it causes patients to

scratch their skin "raw," have trouble sleeping, and, rarely, even to commit suicide.
It is the disease causing the jaundice that causes most problems associated with jaundice. Specifically, if
the jaundice is due to liver disease, the patient may have symptoms or signs of liver disease or cirrhosis.
(Cirrhosisrepresents advanced liver disease.) The symptoms and signs of liver disease and cirrhosis
include fatigue, swelling of the ankles, muscle wasting,ascites (fluid accumulation in the abdominal
cavity), mental confusion orcoma, and bleeding into the intestines.
If the jaundice is caused by blockage of the bile ducts, no bile enters the intestine. Bile is necessary for
digesting fat in the intestine and releasing vitamins from within it so that the vitamins can be absorbed
into the body. Therefore, blockage of the flow of bile can lead to deficiencies of certain vitamins. For
example, there may be a deficiency of vitamin K that prevents proteins that are needed for normal clotting
of blood to be made by the liver, and, as a result, uncontrolled bleeding may occur.

What diseases cause jaundice?

Increased production of bilirubin
There are several uncommon conditions that give rise to over-production of bilirubin. The bilirubin in the
blood in these conditions usually is only mildly elevated, and the resultant jaundice usually is mild and
difficult to detect. These conditions include: 1) rapid destruction of red blood cells (referred to as
hemolysis), 2) a defect in the formation of red blood cells that leads to the over-production of hemoglobin
in the bone marrow (called ineffective erythropoiesis), or 3) absorption of large amounts of hemoglobin
when there has been much bleeding into tissues (e.g., from hematomas, collections of blood in the
tissues).
Acute inflammation of the liver
Any condition in which the liver becomes inflamed can reduce the ability of the liver to conjugate (attach
glucuronic acid to) and secrete bilirubin. Common examples include acute viral hepatitis, alcoholic
hepatitis, and Tylenol-induced liver toxicity.
Chronic liver diseases
Chronic inflammation of the liver can lead to scarring and cirrhosis, and can ultimately result in jaundice.
Common examples include chronic hepatitis Band C, alcoholic liver disease with cirrhosis, and
autoimmune hepatitis.
Infiltrative diseases of the liver refer to diseases in which the liver is filled with cells or substances that
don't belong there. The most common example would be metastatic cancer to the liver, usually from
cancers within the abdomen. Uncommon causes include a few diseases in which substances accumulate
within the liver cells, for example, iron (hemochromatosis), alpha-one antitrypsin (alpha-one antitrypsin
deficiency), and copper (Wilson's disease).

Inflammation of the bile ducts

Diseases causing inflammation of the bile ducts, for example, primary biliary cirrhosis or sclerosing
cholangitis and some drugs, can stop the flow of bile and elimination of bilirubin and lead to jaundice.
Blockage of the bile ducts
The most common causes of blockage of the bile ducts are gallstones andpancreatic cancer. Less common
causes include cancers of the liver and bile ducts.
Drugs
Many drugs can cause jaundice and/or cholestasis. Some drugs can cause liver inflammation (hepatitis)
similar to viral hepatitis. Other drugs can cause inflammation of the bile ducts, resulting in cholestasis
and/or jaundice. Drugs also may interfere directly with the chemical processes within the cells of the liver
and bile ducts that are responsible for the formation and secretion of bile to the intestine. As a result, the
constituents of bile, including bilirubin, are retained in the body. The best example of a drug that causes
this latter type of cholestasis and jaundice is estrogen. The primary treatment for jaundice caused by drugs
is discontinuation of the drug. Almost always the bilirubin levels will return to normal within a few
weeks, though in a few cases it may take several months.
Genetic disorders
There are several rare genetic disorders present from birth that give rise to jaundice. Crigler-Najjar
syndrome is caused by a defect in the conjugation of bilirubin in the liver due to a reduction or absence of
the enzyme responsible for conjugating the glucuronic acid to bilirubin. Dubin-Johnson and Rotor's
syndromes are caused by abnormal secretion of bilirubin into bile.
The only common genetic disorder that may cause jaundice is Gilbert's syndrome which affects
approximately 7% of the population. Gilbert's syndrome is caused by a mild reduction in the activity of
the enzyme responsible for conjugating the glucuronic acid to bilirubin. The increase in bilirubin in the
blood usually is mild and infrequently reaches levels that cause jaundice. Gilbert's syndrome is a benign
condition that does not cause health problems.
Developmental abnormalities of bile ducts
There are rare instances in which the bile ducts do not develop normally and the flow of bile is
interrupted. Jaundice frequently occurs. These diseases usually are present from birth though some of
them may first be recognized in childhood or even adulthood. Cysts of the bile duct (choledochal cysts)
are an example of such a developmental abnormality. Another example is Caroli's disease.
Jaundice of pregnancy Most of the diseases discussed previously can affect women during pregnancy,
but there are some additional causes of jaundice that are unique to pregnancy.
Cholestasis of pregnancy is an uncommon condition that occurs in pregnant women during the third
trimester. The cholestasis is often accompanied by itching but infrequently causes jaundice. The itching
can be severe, but there is treatment (ursodeoxycholic acid or ursodiol). Pregnant women with cholestasis

usually do well although they may be at greater risk for developing gallstones. More importantly, there
appears to be an increased risk to the fetus for developmental abnormalities. Cholestasis of pregnancy is
more common in certain groups, particularly in Scandinavia and Chile, and tends to occur with each
additional pregnancy. There also is an association between cholestasis of pregnancy and cholestasis
caused by oral estrogens, and it has been hypothesized that it is the increased estrogens during pregnancy
that are responsible for the cholestasis of pregnancy.

Pre-eclampsia. previously called toxemia of pregnancy, is a disease that occurs during the second half of
pregnancy and involves several systems within the body, including the liver. It may result in high blood
pressure, fluid retention, and damage to the kidneys as well as anemia and reduced numbers of platelets
due to destruction of red blood cells and platelets. It often causes problems for the fetus. Although the
bilirubin level in the blood is elevated in pre-eclampsia, it usually is mildly elevated, and jaundice is
uncommon. Treatment of pre-eclampsia usually involves delivery of the fetus as soon as possible if the
fetus is mature.
Acute fatty liver of pregnancy is a very serious complication of pregnancy of unclear cause that often is
associated with pre-eclampsia. It occurs late in pregnancy and results in failure of the liver. It can almost
always be reversed by immediate delivery of the fetus. There is an increased risk of infant death. Jaundice
is common, but not always present in AFLP. Treatment usually involves delivery of the fetus as soon as
possible.

What is neonatal jaundice (jaundice in newborn infants)?

Neonatal jaundice is jaundice that begins within the first few days after birth. (Jaundice that is present at
the time of birth suggests a more serious cause of the jaundice.) In fact, bilirubin levels in the blood
become elevated in almost all infants during the first few days following birth, and jaundice occurs in
more than half. For all but a few infants, the elevation and jaundice represents a normal physiological
phenomenon and does not cause problems.
The cause of normal, physiological jaundice is well understood. During life in the uterus, the red blood
cells of the fetus contain a type of hemoglobin that is different than the hemoglobin that is present after
birth. When an infant is born, the infant's body begins to rapidly destroy the red blood cells containing the
fetal-type hemoglobin and replaces them with red blood cells containing the adult-type hemoglobin. This
floods the liver with bilirubin derived from the fetal hemoglobin from the destroyed red blood cells. The
liver in a newborn infant is not mature, and its ability to process and eliminate bilirubin is limited. As a
result of both the influx of large amounts of bilirubin and the immaturity of the liver, bilirubin
accumulates in the blood. Within two or three weeks, the destruction of red blood cells ends, the liver
matures, and the bilirubin levels return to normal.